The aim of this proposal is to determine the role of two forebrain circumventricular organs, the subfornicalorgan (SFO) and the organum vasculosum laminae terminalis (OVLT), and the nucleus preopticus medianus (POME) in the regulation of water balance in the dog. Experiments to evaluate responsiveness of mechanisms causing drinking and serection of arginine vasopressin (AVP) induced by hypertonic NaCl, angiotensin II (AII), hemorrhage and water deprivation will be conducted before and after making discrete lesions of the VFO, OVLT or POME. Long-term balance studies employing daily measurements of body weight, food and water intake and urine output, plasma levels of AVP, sodium, osmolality and plasma renin activity combined with frequent determination of plasma and extracellular fluid volumes conducted before and after lesioning the SEO, OVLT or POME will provide necessary data to evaluate the importance of these structures in the daily regulation of water and sodium balance. The same protocols will be used to evaluate effects of knife cuts designed to interrupt connections between the SFO and POME and between the OVLT and the POME. Neural connectivity of these structures will be determined by injecting retrograde and antegrade tracers into each site. In other experiments electrophysiologic methods will be used to determine if AII and osmosensitive elements are located in the SFO and OVLT. The combination of data obtained in lesion, knife cut, tracing and electrophysiologic studies will provide a ore complete picture of the functional role of the SFO, OVLT and POME in the regulation of water balance. Additional experiments will be carried out to determine the effect of lesions of the SFO and OVLT on the disturbances in fluid and electrolyte balance caused by thoracic vena caval constriction. These studies will provide information on whether forebrain structures are involved in the etiology of disordered water balance in this model of congestive heart failure and its pathological consequences.